Peripheral Nervous System: Organization and Neurotransmitters

Learning Objectives

• Outline the organisation of the nervous system and its divisions
• Define afferent and efferent pathways
• Describe the function of the sympathetic and the parasympathetic nervous system
• How do they maintain homeostasis?
• Explain the affect of neurotransmitters released by sympathetic and parasympathetic nerves
• Consider the tissues/organs and response from neurotransmitter binding
• What are the normal responses/activity controlled by the sympathetic and the parasympathetic?
• Describe how release of hormone adrenaline during "stress" would impact on the sympathetic pathway
• Outline how drugs exert their actions on the PNS

Readings

• Craft et al (2022) Understanding Pathophysiology 4th Edition, Elsevier Australia: chapter 6, pages 96-105, 125-132
• Burchum et al (2019) Lehne's Pharmacology for Nursing Care, Saunders Elsevier: chapter 13, pages 105-117

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Lecture Outline

• Recap the nervous system
• Divisions
• Neural cells
• Action potentials
• Neurotransmission
• Neurotransmitters
• Receptors
• Parasympathetic and Sympathetic nervous system
• Anatomy
• Function
• Receptors

Nervous System Recap

• Regulates, coordinates and drives other systems of the body
• Controls activities of the internal organs
• Receives, processes and responds to information from the external environment

Brain e.g. sensory information about the body and our environment e.g. commands Body

Divisions of the Nervous System

Cerebrum Brain Cerebellum Brain stem Central nervous system Brain Spinal cord Central Nervous System Brainstem Spinal cord Peripheral nervous system Nervous System Somatic Nervous System Skin, Joints & Muscles Peripheral Nervous System Autonomic Nervous System Organs, Blood vessels & Glands Figure: 1.7, Bear et al., Neuroscience: Exploring the Brain 3rd Ed, 2007

Central and Peripheral Nervous Systems

• An integrated system Central Nervous system e.g. sensory information about the body and our environment e.g. commands Peripheral Nervous system
• Specific terminology is used to describe the direction of information flow through the nervous system
• Afferent: information travelling towards a structure Efferent: information travelling away from a structure

Autonomic Nervous System

Somatic nervous system Enteric Nervous system Neurons of the digestive tract Peripheral Nervous System Autonomic Nervous System Sympathetic Nervous system "Fight or flight or fright" Parasympathetic nervous system "Rest and digest"

Neurons

• Two cell classes of neuronal cells:
• Neurons - primary cell
• Neuroglia - support
• Basic features:
• Cell body (soma)
• Dendrites - receive information, "antennae"
• Axons - carry information, "cable"
• Classification:
• Structural - unipolar, bipolar, multipolar etc.
• Functional - Motoneuron, Sensory neuron
• Function:
• Detect stimuli
• Signalling via action potentials

A Dendrites -Cell body -Nucleus Red arrows = direction of signal Axon -Myelin sheath Node of Ranvier Axon terminal B

Excitatory Membrane

Figure: 6.3, page 98, Craft & Gordon, 'Understanding Pathophysiology', 2022An excitatory membrane

• Covered in a plasma membrane
• Inside the cell more negative than outside
• Resting membrane potential (-70 mV). outside cell [K +] 5 mM [Na+] 150 mM [Cl- ] 120 mM + + + + + 555 I I I - inside cell [K+] 140 mM [Na+] 15 mM [Cl- ] 10 mM [A-] 100 mM [K+] = potassium ion concentration [Na+] = sodium ion concentration [Cl- ] = chloride ion concentration [A]] = other anions -70 -30 0 EXTRACELLULAR FLUID +30 mV + + + + + + Plasma membrane - - CYTOSOL Outside cell Phospholipid bilayer Inside cell Figure: 3.3, Bear et al., Neuroscience: Exploring the Brain 3rd Ed, 2007. Fig. 12-8 Fundamentals of Anatomy & Physiology, Martini et al (2018) Courtesy Pearson Education Inc

Action Potential

• If the membrane potential reaches threshold (-60 mV) -> Action potential
• Moves down the axon towards the axon terminal
• "All or none" response Action Potential:
  1. Resting membrane potential (-70 mV)
  2. Stimuli cause graded potentials. If depolarise membrane to -60 mV, voltage-gated Sodium channels open, Na+ moves in
  3. At 30 mV, voltage-gated Potassium channels open, Na-channels close. K+ moves out. Repolarisation occurs
  4. Hyperpolarisation occurs. Return to resting potential
  B +30 3 K+ exits neuron Membrane potential (millivolts) 0 Na+ enters neuron Rest Return to rest 2 -70 Postsynaptic neuron Axon terminals Undershoot of K+ exit Time (milliseconds) Figure: 6.7B, page 101, Craft & Gordon, 'Understanding Pathophysiology', 2022 Fig. 12-2 Fundamentals of Anatomy & Physiology, Martini et al (2015) Courtesy Pearson Education Inc

Stimulus Dendrites Resting potential Action potential Axon hillock May produce Axon Presynaptic neuron 1 4

Neurotransmission

• Once action potential reaches axon terminal > Neurotransmission
• Also called synaptic signalling/synaptic transmission
• Presynaptic neuron signals to postsynaptic neuron/tissue Neurotransmission:
  1. Action potential arrives at axon terminal
  2. Voltage-gated Calcium channels open, Ca2+ moves into the cell
  3. Synaptic vesicles moves to the plasma membrane
  4. Vesicles release neurotransmitter into the synaptic cleft
  5. Neurotransmitter binds receptor on the postsynaptic neuron/tissue
  1 Action potential 2 Ca2+ entry 3 Ca 2+ Synaptic cleft Axon of presynaptic neuron Vesicles move Neurotransmitter 4 Neurotransmitter release 5 Neurotransmitter binds to receptors Dendrite of postsynaptic neuron Figure: 6.8, page 102, Craft & Gordon, 'Understanding Pathophysiology', 2022

Neurotransmitters

• Signalling chemicals
• More than 50 identified
• Act as a ligand
• Highly specific binding to specific receptors
• Lock-and-key mechanism
• Neurotransmitter-receptor binding results in signal transduction
• Excitatory or inhibitory
• Response dependant on neurotransmitter type and receptor type

Types of Neurotransmitters

TABLE 6.4 Common neurotransmitters SUBSTANCE LOCATION EFFECT CLINICAL EXAMPLE Acetylcholine Many parts of the brain, spinal cord, neuromuscular junction of skeletal muscle and many autonomic nervous system synapses Excitatory or inhibitory Alzheimer's disease (a type of dementia) is associated with a decrease in acetylcholine- secreting neurons. Noradrenaline and adrenaline (known as norepinephrine and epinephrine in United States) Many areas of the brain and spinal cord; also in some autonomic nervous system synapses Excitatory or inhibitory Cocaine and amphetamines, resulting in overstimulation of postsynaptic neurons. Serotonin Many areas of the brain and spinal cord Generally inhibitory Involved with mood, anxiety and sleep induction. Levels of serotonin are elevated in schizophrenia (delusions, hallucinations, withdrawal). Dopamine Some areas of the brain Generally excitatory Parkinson's disease (depression of voluntary motor control) results from destruction of dopamine-secreting neurons. Drugs used to increase dopamine production may induce schizophrenia. Gamma-aminobutyric acid (GABA) Most neurons of the central nervous system Inhibitory Drugs that increase GABA function have been used to treat epilepsy (excessive discharge of neurons). Glutamate and aspartate Widespread in the brain and spinal cord Excitatory Drugs that block glutamate or aspartate may prevent seizures and neural degeneration from overexcitation. Endorphins and encephalin Widely distributed in the central and peripheral nervous systems Generally inhibitory Opiates such as morphine and heroin bind to endorphin and encephalin receptors on presynaptic neurons and reduce pain by blocking the release of neurotransmitters. Substance P Spinal cord, brain and sensory neurons associated with pain; digestive tract Generally excitatory Substance P is a neurotransmitter in pain transmission pathways. Blocking the release of substance P by morphine reduces pain. Table 6.4, page 105, Craft & Gordon, 'Understanding Pathophysiology', 2022

Neurotransmitter Receptors

• Located on the membrane of postsynaptic cells
• Many different types, named by the type of neurotransmitter they bind.
• The "lock" that receives the "key"
• Ligand (neurotransmitter) binding brings about a change
• Receptors class:
• Channel-linked receptors: fast acting
• G-protein coupled receptors: slower and longer lasting action

Channel-Linked Receptors

• Fast acting
• Transmembrane channels
• "closed" without ligand
• Remain open while ligand (neurotransmitter) binds Channel-linked receptors
  1. Neurotransmitter binds
  2. Receptor changes shape
  3. Creates a central channel
  4. Ions pass into the cell
  lon flow blocked lons flow Ligand Closed ion channel Open ion channel 2013 Pearson Education, Inc. Figure: 11.19, page 441, Marieb & Hoehn, Human Anatomy and Physiology, 2016

G-Protein Coupled Receptors

• Indirect, slow and prolonged
• Transmembrane complexes
• Activate an effector protein
• lon channel
• Enzyme - creates a secondary messenger
• Secondary messenger change an ion channel or cellular metabolism G-protein coupled receptors
  1. Neurotransmitter binds
  2. Activates G-protein
  3. G-protein moves to effector protein
  4. Activates effector protein
  G-protein-gated ion channel Receptor Neurotransmitter G-protein Receptor Neurotransmitter Enzyme G-protein Second messengers Figure: 5.16, Bear et al., Neuroscience: Exploring the Brain 3rd Ed, 2007.